Abstract

Background

The indigenous gut microbiota are thought to play a crucial role in the development
and maintenance of the abnormal inflammatory responses that are the hallmark of inflammatory
bowel disease. Direct tests of the role of the gut microbiome in these disorders are
typically limited by the fact that sampling of the microbiota generally occurs once
disease has become manifest. This limitation could potentially be circumvented by
studying patients who undergo total proctocolectomy with ileal pouch anal anastomosis
(IPAA) for the definitive treatment of ulcerative colitis. A subset of patients who
undergo IPAA develops an inflammatory condition known as pouchitis, which is thought
to mirror the pathogenesis of ulcerative colitis. Following the development of the
microbiome of the pouch would allow characterization of the microbial community that
predates the development of overt disease.

Results

We monitored the development of the pouch microbiota in four patients who underwent
IPAA. Mucosal and luminal samples were obtained prior to takedown of the diverting
ileostomy and compared to samples obtained 2, 4 and 8 weeks after intestinal continuity
had been restored. Through the combined analysis of 16S rRNA-encoding gene amplicons,
targeted 16S amplification and microbial cultivation, we observed major changes in
structure and function of the pouch microbiota following ileostomy. There is a relative
increase in anaerobic microorganisms with the capacity for fermentation of complex
carbohydrates, which corresponds to the physical stasis of intestinal contents in
the ileal pouch. Compared to the microbiome structure encountered in the colonic mucosa
of healthy individuals, the pouch microbial community in three of the four individuals
was quite distinct. In the fourth patient, a community that was much like that seen
in a healthy colon was established, and this patient also had the most benign clinical
course of the four patients, without the development of pouchitis 2 years after IPAA.

Conclusions

The microbiota that inhabit the ileal-anal pouch of patients who undergo IPAA for
treatment of ulcerative colitis demonstrate significant structural and functional
changes related to the restoration of fecal flow. Our preliminary results suggest
once the pouch has assumed the physiologic role previously played by the intact colon,
the precise structure and function of the pouch microbiome, relative to a normal colonic
microbiota, will determine if there is establishment of a stable, healthy mucosal
environment or the reinitiation of the pathogenic cascade that results in intestinal
inflammation.